This research focuses on behavioral markers that may be associated with, and perhaps predict, increased risk for stimulant or alcohol abuse among groups of women. We will continue to use established laboratory methods to assess vulnerability (based on subjective effects and performance effects) and we will add laboratory measures of stress, impulsivity and risk-taking. We will study groups of women (Experimental groups) thought to have underlying vulnerabilities to stress or impulsivity and assess their response to alcohol and the stimulant d-amphetamine (AMPH) relative to matched control groups. We will also conduct a parallel study in men. The 4 groups of women have been selected for one of two reasons: 1) the risk factor is present and prevalent in both males and females, but the overwhelming majority of research studies have been conducted in males (Studies 1 and 2); or 2) the risk factor of interest occurs predominantly in females (Studies 3 and 4). We will initially analyze how a single risk factor of a paternal history of alcoholism (FHP; Study 1) or current moderate drinking (MD; Study 2) affects measures predictive of vulnerability to drug abuse. Our next step will be to determine how multiple risk factors affect measures predictive of vulnerability to drug abuse. Women with a history of childhood sexual abuse (CSA; Study 3) and women with the eating disorder bulimia nervosa (BN; Study 4) are expected to have additional risk factors, such as family histories of alcoholism and/or current moderate drinking. Study 5 will be conducted in men (either FHP or MD) and matched male controls, which will allow us to directly address sex differences in one group of at-risk individuals. In each Study, placebo, 2 doses of AMPH and 2 doses of alcohol will be tested and sessions will be conducted during the follicular phase of the menstrual cycle in females. For each group of high-risk individuals we will determine if there are differences between the experimental group and the matched control group on: 1) Baseline impulsivity measures and cortisol levels; 2) Behavioral, physiological or cortisol response to a social psychological stressor (Trier Social Stress Test); 3) Performance or mood measures following AMPH and alcohol administration; 4) Abuse liability measures, i.e., reinforcing effects, following AMPH and alcohol administration; and 5) Impulsivity or risk-taking measures following AMPH and alcohol administration. This research will provide information about the possible behavioral markers, including measures of stress, impulsivity and risk-taking, which may influence the likelihood that specific groups of high-risk individuals will abuse stimulants and alcohol. This careful characterization will provide important information for prevention strategies and guide drug abuse treatment in these groups of individuals. [unreadable] [unreadable]